Mutagenetix > Incidental Mutations

Incidental Mutation 'R7077:Mdc1'

549303

Institutional Source

Beutler Lab

Gene Symbol

Mdc1

Ensembl Gene

ENSMUSG00000061607

Gene Name

mediator of DNA damage checkpoint 1

Synonyms

NFBD1

MMRRC Submission

Accession Numbers

Is this an essential gene?

Probably essential (E-score: 0.938) question?

Stock #

R7077 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

35841515-35859670 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 35845947 bp

Zygosity

Heterozygous

Amino Acid Change

Alanine to Aspartic acid at position 82 (A82D)

Ref Sequence

ENSEMBL: ENSMUSP00000133568 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000082337] [ENSMUST00000174124]

Predicted Effect

probably damaging
Transcript: ENSMUST00000082337
AA Change: A82D

PolyPhen 2 Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000080949
Gene: ENSMUSG00000061607
AA Change: A82D

Domain	Start	End	E-Value	Type
low complexity region	12	18	N/A	INTRINSIC
FHA	53	105	5.63e-9	SMART
low complexity region	194	215	N/A	INTRINSIC
low complexity region	854	870	N/A	INTRINSIC
low complexity region	969	987	N/A	INTRINSIC
low complexity region	1008	1022	N/A	INTRINSIC
internal_repeat_1	1027	1115	6.7e-11	PROSPERO
internal_repeat_2	1030	1141	2.36e-9	PROSPERO
internal_repeat_1	1266	1354	6.7e-11	PROSPERO
internal_repeat_2	1298	1417	2.36e-9	PROSPERO
low complexity region	1422	1445	N/A	INTRINSIC
low complexity region	1457	1477	N/A	INTRINSIC
BRCT	1502	1579	1.66e-1	SMART
BRCT	1612	1691	2.45e1	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000174124
AA Change: A82D

PolyPhen 2 Score 0.969 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000133568
Gene: ENSMUSG00000061607
AA Change: A82D

Domain	Start	End	E-Value	Type
low complexity region	12	18	N/A	INTRINSIC
FHA	53	105	5.63e-9	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000225192

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

98% (54/55)

MGI Phenotype

FUNCTION: The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 7 divergent copies of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci. Mice with mutations in this gene exhibit growth retardation, male infertility, immune defects, chromosome instability, DNA repair defects, and radiation sensitivity. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutant mice are smaller and display increased susceptibility to ionizing radiation, male infertility, T and B cell abnormalities, and increased genomic instability. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 53 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam21	C	T	12: 81,559,119	C623Y	probably damaging	Het
Ago3	T	C	4: 126,371,532	K322R	probably null	Het
Ankrd17	T	C	5: 90,285,864	H682R	possibly damaging	Het
Aoah	A	G	13: 20,910,106	D187G	probably damaging	Het
Arhgap17	T	C	7: 123,280,008	D840G	unknown	Het
AW551984	C	T	9: 39,591,427	V650I	probably benign	Het
BC051142	C	A	17: 34,440,882	T93N	possibly damaging	Het
Bok	T	A	1: 93,689,189	Y86N	probably damaging	Het
Ccdc146	T	A	5: 21,305,274	N580I	possibly damaging	Het
Ccng2	T	C	5: 93,269,340	S72P	possibly damaging	Het
Cfap74	T	G	4: 155,455,677	I977S	unknown	Het
Cobl	T	C	11: 12,253,441	N1087S	probably benign	Het
Cyp21a1	C	A	17: 34,802,359	R346L	probably damaging	Het
Eif4a1	A	C	11: 69,670,664	F52L	probably damaging	Het
Eif4ebp2	A	C	10: 61,433,801	I120S	probably damaging	Het
Enpp2	A	C	15: 54,901,391	D146E	probably benign	Het
Exosc9	T	C	3: 36,553,056	Y30H	probably damaging	Het
Fam117a	G	A	11: 95,377,672	G300S	probably benign	Het
Focad	C	A	4: 88,410,677	A1709E	unknown	Het
Fsd1	G	A	17: 55,993,876	R245H	probably damaging	Het
Fsip2	T	C	2: 82,983,152	F3272L	probably benign	Het
Gcnt2	G	A	13: 40,860,420	M22I	probably benign	Het
Gjd4	T	C	18: 9,280,928	E50G	probably damaging	Het
Gm10375	G	T	14: 43,602,970	T162K	probably benign	Het
Gm10837	C	G	14: 122,490,730	A6G	unknown	Het
Gm4924	T	C	10: 82,379,223	F952L	unknown	Het
Heatr1	T	C	13: 12,418,164	F1132L	possibly damaging	Het
Hnrnpu	A	G	1: 178,332,191	Y442H	unknown	Het
Hp1bp3	C	A	4: 138,239,618	T408N	probably damaging	Het
Htra3	A	G	5: 35,668,316	V198A	probably damaging	Het
Katnal1	T	C	5: 148,891,737	T300A	probably benign	Het
Lipo5	G	T	19: 33,467,770	P133Q		Het
Lrp1b	A	T	2: 41,770,846	H197Q		Het
Mstn	A	T	1: 53,064,249	D248V	probably benign	Het
Myo1d	C	T	11: 80,674,634	E426K	probably damaging	Het
Ola1	G	A	2: 73,141,964	T221I	probably damaging	Het
Olfr1086	T	C	2: 86,676,892	Y147C	possibly damaging	Het
Olfr67	A	G	7: 103,787,386	I297T	probably damaging	Het
Olfr857	T	A	9: 19,713,132	S102T	probably benign	Het
Olfr898	T	A	9: 38,349,970	Y290N	probably damaging	Het
Phldb1	T	C	9: 44,711,904	T618A	possibly damaging	Het
Pkd1	T	G	17: 24,591,119	W3565G	probably damaging	Het
Prl3a1	A	T	13: 27,276,103	N190I	probably benign	Het
Ptk2	G	A	15: 73,221,809	P854S	possibly damaging	Het
Ptpn11	C	T	5: 121,143,570	R484Q	probably benign	Het
Rapgef4	T	C	2: 72,241,476	M900T	probably damaging	Het
Slc1a2	A	T	2: 102,777,510	D501V	probably benign	Het
Smarcd3	G	T	5: 24,594,962	A270D	probably damaging	Het
Srgap2	A	G	1: 131,344,449	M33T		Het
Tle1	G	C	4: 72,158,375	P139A	probably benign	Het
Tmem161b	C	A	13: 84,222,418		probably benign	Het
Zfp658	T	A	7: 43,573,989	S563T	probably benign	Het
Zswim9	G	A	7: 13,259,752	R826C	probably damaging	Het

Other mutations in Mdc1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01473:Mdc1	APN	17	35848020	missense	probably benign	0.04
IGL01662:Mdc1	APN	17	35852505	missense	probably benign	0.00
IGL01931:Mdc1	APN	17	35848231	missense	probably benign	0.00
IGL02542:Mdc1	APN	17	35853156	missense	probably damaging	0.96
IGL02823:Mdc1	APN	17	35852923	missense	probably damaging	0.99
IGL03411:Mdc1	APN	17	35853126	missense	probably benign	0.06
IGL02799:Mdc1	UTSW	17	35846191	missense	possibly damaging	0.86
PIT4362001:Mdc1	UTSW	17	35844469	missense	possibly damaging	0.72
R0054:Mdc1	UTSW	17	35849033	missense	probably benign	0.00
R0129:Mdc1	UTSW	17	35854445	missense	probably benign	0.04
R0131:Mdc1	UTSW	17	35852581	missense	probably damaging	0.99
R0131:Mdc1	UTSW	17	35852581	missense	probably damaging	0.99
R0132:Mdc1	UTSW	17	35852581	missense	probably damaging	0.99
R1406:Mdc1	UTSW	17	35853532	missense	probably benign	0.10
R1406:Mdc1	UTSW	17	35853532	missense	probably benign	0.10
R1597:Mdc1	UTSW	17	35845866	missense	probably damaging	1.00
R1721:Mdc1	UTSW	17	35847826	missense	possibly damaging	0.85
R1888:Mdc1	UTSW	17	35854225	missense	probably benign	0.03
R1888:Mdc1	UTSW	17	35854225	missense	probably benign	0.03
R1912:Mdc1	UTSW	17	35844538	missense	probably benign	0.00
R1912:Mdc1	UTSW	17	35850811	missense	probably benign	0.19
R1977:Mdc1	UTSW	17	35850930	missense	probably benign	0.01
R2121:Mdc1	UTSW	17	35847943	missense	probably benign	0.03
R2122:Mdc1	UTSW	17	35847943	missense	probably benign	0.03
R2357:Mdc1	UTSW	17	35847445	missense	probably benign	0.00
R2842:Mdc1	UTSW	17	35848794	missense	probably benign	0.01
R2851:Mdc1	UTSW	17	35849010	missense	probably benign	0.04
R2852:Mdc1	UTSW	17	35849010	missense	probably benign	0.04
R2964:Mdc1	UTSW	17	35853637	missense	possibly damaging	0.72
R2996:Mdc1	UTSW	17	35847893	unclassified	probably benign
R3752:Mdc1	UTSW	17	35845929	missense	probably damaging	1.00
R4234:Mdc1	UTSW	17	35848824	missense	probably benign	0.00
R4641:Mdc1	UTSW	17	35857469	missense	probably benign	0.09
R4706:Mdc1	UTSW	17	35852779	missense	probably damaging	0.99
R4809:Mdc1	UTSW	17	35849101	critical splice donor site	probably null
R4833:Mdc1	UTSW	17	35850394	missense	probably benign	0.20
R5032:Mdc1	UTSW	17	35850589	missense	probably benign	0.00
R5047:Mdc1	UTSW	17	35847844	missense	probably benign	0.00
R5086:Mdc1	UTSW	17	35848630	missense	probably benign	0.00
R5172:Mdc1	UTSW	17	35853090	missense	probably benign	0.00
R5254:Mdc1	UTSW	17	35847922	missense	probably benign	0.00
R5473:Mdc1	UTSW	17	35848060	missense	probably benign	0.01
R5550:Mdc1	UTSW	17	35845884	missense	possibly damaging	0.64
R5561:Mdc1	UTSW	17	35848546	missense	probably benign	0.00
R5888:Mdc1	UTSW	17	35847820	missense	probably benign	0.01
R6020:Mdc1	UTSW	17	35848633	missense	probably benign	0.04
R6020:Mdc1	UTSW	17	35857572	missense	probably benign	0.01
R6219:Mdc1	UTSW	17	35850674	missense	probably benign	0.10
R7053:Mdc1	UTSW	17	35846326	missense	probably benign	0.00
R7073:Mdc1	UTSW	17	35854068	missense	probably benign	0.18
R7424:Mdc1	UTSW	17	35853309	missense	probably benign	0.04
R7443:Mdc1	UTSW	17	35850820	missense	probably damaging	0.98
R7467:Mdc1	UTSW	17	35844556	missense	probably benign	0.29
R7549:Mdc1	UTSW	17	35848857	missense	probably null	0.04
R7655:Mdc1	UTSW	17	35850881	missense	probably benign	0.01
R7656:Mdc1	UTSW	17	35850881	missense	probably benign	0.01
RF025:Mdc1	UTSW	17	35854407	critical splice acceptor site	probably benign
X0022:Mdc1	UTSW	17	35850937	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- AACGCCTGTAAGAGCTCTGAG -3'
(R):5'- TTAGAAGACTCCGAGGGACC -3'

Sequencing Primer
(F):5'- TCTGAGTGAGCAGTAGGGTATCTAAC -3'
(R):5'- CCAAGGGTGGTGGGACATC -3'

Posted On

2019-05-15